Emory Parkinson's Disease Collaborative Environmental Research Center (PD-CERC). Building upon the past successes of the Emory University Collaborative Center for Parkinson's Disease Research, we propose an integrated and collaborative center that is aimed at understanding how environmental toxicants, such as pesticides, contribute to the pathogenesis of arkinson's disease. Over the past several years our research groups have identified key mechanisms that appear to be involved in the onset and progression of PD, especially those triggered by environmental factors. The goal of our center is to better understand how environmental toxicants disrupt dopamine homeostasis, mitochondrial function, and redox balance n the substantia nigra, and how the affected neurons respond to these insults. Since many of these perturbations are not restricted to the nigrostriatal dopamine system or even the brain, there is an exciting opportunity to identify peripheral biomarkers of these processes in the serum of oatients using novel metabolomic methods. The overall theme of the center is that environmental toxicants, such as pesticides, act through specific molecular targets to disrupt redox state;and it is the inherent ability of the neurons to defend against these changes that dictate whether the neurons affected in Parkinson's disease survive or die. The PD-CERC has five major objectives: 1. to determine how environmental and genetic disruption of dopamine storage leads to oxidative damage, 2. to identify novel mechanisms by which the dopamine neurons respond to mitochondrial dysfunction and oxidative stress, 3. to determine how environmental toxicants disrupt redox balance in cellular and peripheral compartments, 4. to identify novel metabolomic biomarkers of environmental toxicants and idiopathic PD, 5. to enrich the center through recruitment of investigators, stimulation of new ideas, fostering of new projects, and by providing career development to young investigators and 6. To integrate information on mitochondrial dysfunction, dopamine metabolism, and oxidative stress to guide future strategies for the prevention, diagnosis, and treatment of PD. Completion of these objectives will improve our understanding of how environmental toxicants increase the risk of PD and it will lay the foundation for tailoring therapeutic interventions aimed at mitigating the adverse effects of environmental exposures in PD.